We plan to isolate, partially purify and characterize the enzymes from the trypanosomid flagellate, Crithidia fasciculata, which carry out the de novo synthesis and interconversions of nucleic acid pyrimidines. In addition enzymes of the pyrimidine salvage mechanisms will be studied. Mechanisms of metabolic enzyme control will be investigated in detail. Various inhibitors of the pyrimidine metabolizing enzymes will be used to obtain information regarding active sites. In addition the pyrimidine-metabolizing enzymes of the human blood fluke, Schistosoma mansoni will be studied for comparative purposes and to attempt to discover possibilities for chemotherapeutic attack. The origin of the two carbon fragment of the side chain of biopterin will be studied during its synthesis from 6- hydroxymethylpterin in Crithidia. The involvement of unconjugugatedipteridine cofactors in fatty acid desaturation will be studied. For this both Crithidia and Tetrahymena will be used.